PDGF-C and -D are the major isoforms expressed in human retinal pigment epithelium (RPE). Functionally active PDGFR-α and -β are mainly expressed at the apical membrane. PDGF-BB, -CC, -DD significantly increased proliferation while PDGF-BB, -AB and -DD significantly increased cell migration, suggesting a critical role in RPE pathophysiology. A pro-inflammatory cytokine mixture (TNFα/IL-1β/IFNγ) abrogated PDGF-induced proliferation and migration by inducing apoptosis, and by disrupting the cytoskeleton and tight junctions. Further study demonstrated that IFNγ alone significantly inhibited human fetal RPE (hfRPE) proliferation, which was significantly blocked by JAK inhibitor I, while Type I IFN, IFNα and IFNβ did not affect hfRPE proliferation under the same culture conditions. Addition of IFNγ to the basal, but not the apical bath significantly increased Jv across hfRPE monolayer. In contrast to hfRPE, the proinflammatory cytokine mixture, and IFNγ by itself, stimulated the proliferation of choroidal cells. These findings suggest a complex role of pro-inflammatory cytokines, particularly IFNγ, in overcoming local proliferative/wound healing responses of RPE at the retina/RPE/choroid interface.
| Illek, Beate; Fu, Zhu; Schwarzer, Christian et al. (2008) Flagellin-stimulated Cl- secretion and innate immune responses in airway epithelia: role for p38. Am J Physiol Lung Cell Mol Physiol 295:L531-42 |
| Li, Rong; Maminishkis, Arvydas; Wang, Fei E et al. (2007) PDGF-C and -D induced proliferation/migration of human RPE is abolished by inflammatory cytokines. Invest Ophthalmol Vis Sci 48:5722-32 |
